Restenosis is a major limitation of coronary angioplasty, requiring further intervention in the majority of cases. Intracoronary radiation has been employed in recent years to prevent restenosis lesions with effective results, principally in in-stent restenosis. Restenosis is generally considered as an excessive form of normal wound healing divided up in processes: elastic recoil, neointimal hyperplasia, and negative vascular remodeling. Restenosis has previously been regarded as a proliferative process in which neointimal thickening, mediated by a cascade of inflammatory mediators and other factors, is the key factor. Data from recent studies have pointed to negative vascular remodeling as a major contributing factor. Recent studies have also identified particular cell lines that might be critical regulators of restenosis, particularly monocyte-derived macrophages and myofibroblasts. This review summarizes the current theories of vascular biology pertaining to restenosis in coronary arteries and the potential mechanisms of why radiation may effectively inhibit restenosis.